Differential modes of nuclear localization signal (NLS) recognition by three distinct classes of NLS receptors

The targeting of karyophilic proteins to nuclear pores is mediated via the formation of a nuclear pore-targeting complex, through the interaction of nuclear localization signal (NLS) with its NLS receptor. Recently, a novel human protein, Qip1, was identified from a yeast two-hybrid system with DNA helicase Q1. This study demonstrates that Qip1 is a novel third class of NLS receptor that efficiently recognizes the NLS of the helicase Q1. Moreover, the data obtained in this study show that the specific interaction between Qip1 and the NLS of the helicase Q1 requires its upstream sequence of the minimal essential NLS. By using purified recombinant proteins alone in the digitonin-permeabilized cell-free transport system, it was demonstrated that the two known human NLS receptors, Rch1 and NPI-1, are able to transport all the tested NLS substrates into the nucleus, while Qip1 most efficiently transports the helicase Q1-NLS substrates, which contain its upstream sequence in so far as we have examined the system. Furthermore, in HeLa cell crude cytosol, it was found that endogenous Rch1 binds to all the tested NLS substrates, while the binding of endogenous NPI-1 is restricted to only some NLSs, despite the fact that NPI-1 itself shows binding activity to a variety of NLSs. These results indicate that at least three structurally and functionally distinct NLS receptors exist in the human single cell population, and suggest that the nuclear import of karyophilic proteins may be controlled in a complex manner at the NLS recognition step by the existence of a variety of NLS receptors with various specificities to each NLS.     

Clinical and serological study of tsutsugamushi disease in northern Osumi, Kagoshima Prefecture

We report 34 cases of tsutsugamushi disease seen from 1989 to 1993 at Yagi Clinic, northern Osumi, Kagoshima Prefecture. Nineteen patients (55.9%) showed the highest antibody titers against the Kawasaki strain Orientia tsutsugamushi (Ot) and 13 (38.2%) against the Kuroki strain Ot. It is suggested that two antigenic types (Kawasaki and Kuroki) of Ot were distributed in Kagoshima Prefecture, and the Kawasaki type Ot more or less dominates Kuroki type Ot. There was no difference in clinical features between the two groups of patients.     

A probabilistic method for the design of power grounding systems

An improved multivariable, probabilistic method for the safety analysis of power grounding systems is presented. The application of this method is demonstrated in four examples. The first three examples illustrate the practical evaluation of one new and two existing substation grounding grids when the substation is connected to an overhead distribution system. The fourth example ascertains the relative impact of a difference between the S curve of IEC Publication 479 and Dalziel's equation for the allowable body current used in ANSI/IEEE Std 80-1986 on the validity of an exposure model based on the requirements of Std 80. In this example, the statistical data on ground faults have been taken from actual system records. Further possible refinements of the exposure model are discussed     

A non-specific lipid transfer protein from Arabidopsis is a cell wall protein

Lipid transfer proteins (LTPs), mediate the transfer of phospholipids between membranes in vitro. However, the in vivo function of LTPs is not known. To determine the precise location of a non-specific LTP from Arabidopsis, a cDNA clone was used to produce an Arabidopsis LTP:protein A fusion. Antibodies raised against the fusion were used to localize the Arabidopsis LTP by immunoelectron microscopy. LTP was found to be located in the cell wall, mainly in epidermal cells. This location appears to be inconsistent with the proposed role of the protein in intracellular lipid transfer.     

Magnetic resonance imaging study on the results of surgery for cervical compression myelopathy

The morphologic changes and signal intensity of the spinal cord on preoperative magnetic resonance images were correlated with postoperative outcomes in 74 patients undergoing decompressive cervical surgery for compressive myelopathy. The transverse area of the spinal cord on T1-weighted images at the level of maximum compression was closely correlated with the severity of myelopathy, duration of disease, and recovery rate as determined by the Japanese Orthopaedic Association score. In patients with ossification of the posterior longitudinal ligament or cervical spondylotic myelopathy, the increased intramedullary T2-weighted magnetic resonance imaging signal at the site of maximal cord compression and duration of disease significantly influenced the rate of recovery. A multiple regression equation was then developed with these three variables to predict surgical outcomes.     

Epidemiology of hepatitis C and G in sporadic and familial porphyria cutanea tarda

From 1995 to 1997, we prospectively evaluated the prevalence of hepatitis C virus (HCV) RNA in 124 patients with porphyria cutanea tarda (PCT) from Northern France (83 sporadic and 41 familial PCT). Serum samples were analyzed for ferritin, transaminases, HCV antibodies, and HCV RNA. In addition, genotyping of HCV and searches for HCV infection risk factors (blood transfusion, iv drug abuse, and surgical intervention) were performed. Twenty-six of 124 patients (21%; 95% CI: 13.9-28) were positive for serum HCV antibodies. All of them were also positive for HCV RNA. The prevalence of HCV infection was higher in the sporadic PCT group (26.5%, 22 out of 83) than in the familial PCT group (9.7%, 4 out of 41). Risk factors for hepatitis C infection were found to be significantly increased in the HCV-positive group when compared with the HCV-negative PCT group. In all HCV-positive patients with a risk factor, the suspected date of exposure to the virus always preceded the clinical onset of PCT. The HCV genotype pattern in PCT patients was similar to that observed in nonporphyric HCV patients in western European countries. Serum ferritin level was increased in both HCV-positive and HCV-negative porphyric patients. Transaminase levels were significantly higher in HCV-infected PCT patients. Sixty-seven out of 124 patients were retrospectively studied for hepatitis G virus (HGV) infection. Six of these 67 patients (8.9%; 95% CI: 2.1-15.8) were positive for HGV RNA. None of the six HGV-infected patients were positive for HCV RNA. The HGV-infected patients did not differ statistically from those without HGV infection with regard to age, ferritin, transaminase levels, and PCT treatment. These results support the view that sporadic cases of HGV infection may occur frequently. This study of a large cohort of HCV and PCT patients further documents an increasing gradient in HCV prevalence from northern to southern Europe, and shows that HCV infection acts as a triggering factor of PCT. Finally, the HGV prevalence found in the PCT patients was comparable with that found in French blood donors, suggesting that HGV is not a PCT triggering factor.     

Multiterminal light-emitting logic device electricallyreprogrammable between OR and NAND functions

A monolithic multiterminal logic device that functions both optically and electrically as an ORNAND gate, is demonstrated for the first time. The device, based on the real-space transfer of hot electrons into a complementary collector layer, has been implemented in an InGaAs/InAlAs/InGaAs heterostructure grown by molecular beam epitaxy. Excellent performance is obtained at room temperature. The collector current and the optical output power both exhibit the OR and the NAND functions of any two of the three input terminals, these functions being interchangeable by the voltage on the third terminal     

Effect of type of processing on the microstructural features and mechanical properties of Al-Cu/SiC metal matrix composites

In this study, an aluminum based metallic matrix (Al-2wt.% Cu) was reinforced with SiC particulates using a conventional casting technique and a new disintegrated melt deposition technique. Microstructural characterization studies conducted on the samples taken from disintegrated melt deposition technique revealed a more uniform distribution of SiC particulates and good interfacial integrity between SiC particulates and metallic matrix when compared to the conventionally cast composite samples. Results of ambient temperature mechanical tests demonstrate an increase in 0.2% YS and ultimate tensile strength of samples taken from disintegrated melt deposition technique when compared with the unreinforced and conventionally cast composite samples. The results of microstructural characterization and mechanical testing were finally rationalized in terms of the nature of processing technique employed to reinforce Al-2wt.% Cu metallic matrix with SiC particulates.     

Pharmacodynamic Comparison of a Nasal Formulation of Verapamil and Intravenous and Oral Dosage Forms

The nasal route has been shown to be effective for the administration of numerous drugs in order to improve drug bioavailability. A nasal gel of verapamil hydrochloride was formulated and evaluated pharmacodynamically in humans, using electrocardiographic results, with comparison to oral and IV routes. Seven volunteers were involved in the study and the pharmacodynamic parameters were evaluated statistically. Experimental nasal gel showed similar pharmacodynamic results with the intravenous route, which is a hint to the reduction in verapamilinduced first-pass metabolism. However, oral route of administration showed a tendency of less efficacy. No reasonable effect of verapamil could be obtained with the placebo group.